AACR: Biomarker predicts sensitivity of melanoma to drugs

(HealthDay News) -- Monitoring changes in a biomarker can predict whether a class of melanomas will be sensitive to a particular class of drugs, according to a study presented at the AACR-NCI-EORTC International Conference on Molecular Targets and Cancer Therapeutics, held from Oct. 19 to 23 in Boston.

To identify biomarkers associated with the efficacy of BRAF-targeted melanoma drugs, Ryan B. Corcoran, M.D., Ph.D., from Massachusetts General Hospital in Boston, and colleagues examined the activity of proteins downstream of BRAF in BRAF-mutant melanomas that were sensitive or resistant to the BRAF-targeted drug vemurafenib.

The researchers found that reduced phosphorylation of ribosomal protein S6 was associated with drug sensitivity in BRAF-mutant melanomas both in vitro and in mice. Analysis of tumor biopsies from patients with BRAF-mutant melanomas showed that reduced S6 phosphorylation after treatment was associated with a significant improvement in progression-free survival (hazard ratio, 0.19). Changes in S6 phosphorylation could be monitored in real time in tumor cells in fine-needle aspiration biopsies during the first two weeks of treatment.

"Many of the signaling pathways known to drive various types of cancer regulate phosphorylation of S6, not just the BRAF pathway," Corcoran said in a statement. "Therefore, we are investigating whether S6 phosphorylation could be a biomarker of response to therapies that target these pathways in cancers other than melanoma."

One author is an employee of Genentech, the manufacturer of vemurafenib.